tbuckley/cabot-search huggingface dataset:
Abstract 12520: Advancements in the Treatment of Atherosclerosis
Authors: AHSAN ALI
Journal: Circulation (2023)

Background: Endotheliotoxic hyperlipidemia provide impaired eNOS derived NO production, excessive free-radicals, adhesive molecule generation, vascular lipid accumulation, atherosclerosis development &amp; progression. NO replacement by NO donors can restore NO deficit. HDLs have anti-atherogenic properties and are carriers of excessive cellular cholesterol via reverse cholesterol transport (RCT) pathway. Lipoprotein enrichment by anionic phosphatidylinositol (PI) increases the negative surface potential of lipoproteins and stimulate RCT. PI stimulates rapid flux and clearance of plasma choles-l by increased hepatic uptake. Objective: Regression of atherosclerosis stimulating RCT with experimental combination of NO donor in PI nanocapsules (AlphaX1). Methods: 30 rabbits fed with 2%cholesterol diet for 6 months After 6 m subdivided in 3 groups. G1-10 without treatment. G2-treated with AlphaX1 for 10 days, G3-treated for 20 days. 5 rabbits-control. Animals sacrificed after 10 and 20 days of treatment. Abdominal aorta, part snap frozen in cryostat-OilRedO staining, part exposed for morphology and electron microscopy. Results: Morphology (x100-x27000): G1-numerous vacuoles with neutral lipids and foam cells under endothelium, proliferation of solitary smooth muscle cells containing lipid vacuoles; G2-moderate deposition of lipid vacuoles &amp; foam cells in sub-endothelium, restoration of endothelium. G3-express reduction of lipid vacuoles &amp; foam cells, restoration of elastic fibers, regeneration of endothelium.OilRedO, C 1.4±0.2% G1 38.2±3.6%. G2 7.3±0.8%, G3 2.3±0.6%. Conclusion: Data shows evidence that AlphaX1 provide regeneration of endothelial cells, restoration of elastic fibers (probably due to regulation of fibulin5 by PI3K/Akt), anti-inflammatory effect, clearance of foam cells from neutral lipids and regression of atherosclerosis. AlphaX1 provide antiatherogenic properties of NO and PI, probably by reduction in cytokines production, decrease in adhesion molecules expression, monocyte-endothelium adhesion inhibition, increased cholesterol efflux and plasma clearance via hepatic uptake. AlphaX1 could be a potential new therapeutic agent for prophylaxis &amp; treatment of hyperlipidemia and atherosclerosis.
Abstract 12516: Explaining the Increase Mortality From Cardiovascular Disease in Indonesia: Unraveling the Trends in the Influence of Metabolic and Behavioral Risk Factors (2000-2019)
Authors: Wigaviola Socha Purnamaasri Harmadha, Farizal Rizky Muharram, Renato S Gaspar, Hanif Ardiansyah Sulistya, Zahras Azimuth, Fikri Febrian Firmansyah, Chaq El Chaq Zamzam Multazam, Muhammad Harits, Rendra Mahardika Putra
Journal: Circulation (2023)

Background: CVD burden has shifted from developed to developing countries; it decreased from 48% in 1990 to 43% in 2010, while in developing countries, it increased from 18% to 25%. According to several studies, current behavioural and metabolic risk factors enhance the risk of cardiovascular disease risk. Aims: We investigated whether changes in the risk factors—hyperglycemia, obesity, dyslipidemia, hypertension, and smoking—caused the rise in CVD mortality and incidence from 2000 to 2019 in Indonesia. Methods: Data from 34 province-year observations for CVD outcomes and changes in risk factors between 2000 and 2019 in Indonesia were obtained from IHME. A statistical model calculated risk factor fatalities using population-attributable fractions and baseline year death data. Multivariate regression on Summary Exposure Values of risk factors with mortality and incidence rates and lag year analysis was performed using R, measuring heteroscedasticity-consistent standard errors. Covariates, including the Socio-demographic Index, Primary healthcare, and GDP per capita, were added. Results: The age-standardized mortality rate per 100,000 for CVD from 2000 to 2019 in Indonesia increased from 356 to 412 among men and decreased from 357 to 354 among women. There was an increase in exposure to risk factors; obesity by 9%, smoking by 1%, dyslipidemia by 1.3%, hyperglycemia by 2%, and hypertension by 1.2%. An additional 14,517 men and 17,917 women died from CVD, attributable to obesity. Multivariate regression with province-fixed and year-fixed analysis shows a strong correlation between hyperglycemia in women (6;95% CI 0 to 12) with an increasing death rate in IHD. Notably, the association between hyperglycemia and IHD mortality was regardless of socioeconomic class and healthcare coverage. The association between a 10-year lag of high LDL and incidence of IHD was five times stronger compared to other risk factors, particularly in men (5;95%CI 2 to 8, incidence per 1-point increase). Conclusion: Female hyperglycemia increases CVD mortality risk. However, the prior-year analysis showed that high LDL levels increase incidence in men and women. These findings imply policymakers should prevent high LDL risk factors and hyperglycemia 10 years earlier.
Abstract 15606: Effectiveness and Safety of the Dual Epicardial &amp; Endocardial Procedure (DEEP) Approach for Treatment of Subjects With Persistent or Long Standing Persistent Atrial Fibrillation (PersAF/LSPAF) With Radiofrequency Ablation
Authors: Kenneth Ellenbogen, Ali Khoynezhad, Carlo de Asmundis, Vigneshwar KASIRAJAN, Jayanthi koneru, John Johnkoski, Kevin Rist, Mubashir Mumtaz, Michael Link, Joris R de Groot, Antoine Driessen, Mark Lee, Steven Hoff, David Bello, Gansevoort Dunnington, Susan Eisenberg, Margot Vloka, Benedict Taylor, Stephen Jones, Jonathan Philpott, Thomas Beaver, William Miles, junaid khan, Steven Kang, Gaurang Gandhi, Eric Okum, Nitesh Badhwar, Tina Baykaner, Anson M Lee, Paul A Vesco, J Michael Smith, Sydney Gaynor, Ken Frazier, Mark La Meir
Journal: Circulation (2023)

Background: A collaborative approach between Electrophysiologists (EP) and Cardiothoracic Surgeons (CTS) to effectively target pulmonary veins (PVs) and substrate beyond PVs may improve outcomes for persistent and longstanding persistent AF (PersAF/LSPerAF). Hypothesis: A minimally invasive hybrid approach of bilateral thoracoscopic epicardial ablation and left atrial appendage exclusion (LAAE) with endocardial mapping/ablation (Hybrid approach) is safe and effective to treat advanced AF patients who have failed medical therapy. Aim: DEEP (NCT02393885) aims to establish safety and effectiveness of a Bipolar Radiofrequency (RF) System in a Hybrid approach to treat PersAF/LSPerAF. Methods: DEEP is a prospective, international, single arm trial at 17 sites. Key eligibility: adults with drug refractory PersAF/LSPerAF, left atrial diameter (LAD) ≤5.5cm, failed class I/III AAD, and ≤2 previous failed endocardial catheter ablations (CA). Epicardial surgical ablation included PV isolation, roof and floor lines (posterior LA box), left superior PV to LAA lesion, ganglionic plexi and Ligament of Marshall ablation and LAAE. CA followed 91-121 D post epicardial procedure. After 90 D blanking and 90 D AAD optimization periods, 24-hr rhythm monitoring and ECG were performed 6 and 12 M post CA with symptom driven monitoring between. Primary effectiveness was defined as freedom from atrial arrhythmia (&gt;30 sec) absent new/increased dose of previously failed AAD through 12 M. Safety was device/procedure-related SAEs within 30 D of epicardial ablation and 7 D of CA in all who received anesthesia. Results: Ninety patients were enrolled in 2015-2020, 83.3% PersAF, 16.7% LSPerAF, mean age 63.4±7.74 yrs, 83.3% male, mean BMI 29.9, CHAD2DS2-VASc median 2.0 (1.0, 3.0), 48% failed CA, median AF duration 3.8 yrs, mean LAD 4.5cm. Primary effectiveness 70.6% (60/85; 95% CI 60.9%, 80.3%, p=0.0232) and freedom from AF through 12 M 78.8% (p=0.0002). The adverse event rate was 6.7% (6/90); equal in epi- and endocardial cohort. Both primary endpoints met prespecified success criteria. Conclusion: A collaborative approach between EP and CTS to Hybrid ablation is effective for PersAF/LSerPAF when benefit-risk is deemed favorable, given limited alternative treatments.
Abstract 16909: Eicosapentaenoic Acid and Docosahexaenoic Acid Have Competing Effects on Membrane Lipid Dynamics Due to Differences in Structure
Authors: Samuel C Sherratt, Sandeep Shrivastava, Peter Libby, Deepak L Bhatt, Amitabha Chattopadhyay, Preston Mason
Journal: Circulation (2023)

Background: Omega-3 fatty acids (n3-FAs) incorporate into vascular cell membranes where they modulate protein function and signal transduction. The n3-FA eicosapentaenoic acid (EPA) delivered in ethyl ester form (icosapent ethyl) reduced a broad range of cardiovascular events in high-risk patients (REDUCE-IT). This was not observed with mixed n3-FA formulations containing docosahexaenoic acid (DHA) in STRENGTH and other trials. These discordant outcomes indicate DHA may counter certain EPA effects due to its additional carbons and double bond. We compared these n3-FA effects on membrane lipid dynamics and width, key determinants of protein function. Methods: Membrane lipid fluidity was measured by fluorescence anisotropy approaches in large unilamellar vesicles (LUVs) of 100 nm diameter containing 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC) and 50 mol% cholesterol with EPA and/or DHA (0-10 mol%). LUVs were treated with the fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene (DPH), at 1 mol% and evaluated using a spectrofluorometer with a polarization accessory. Membrane width ( i.e ., unit cell periodicity) of the samples was determined by small angle x-ray scattering (SAXS). Results: DHA alone increased bulk lipid fluidity as indicated by a dose-dependent reduction in apparent rotational correlation time (ARCT); at 10 mol%, there was a ~20% (p&lt;0.05) reduction from ~19 to ~16 nsec compared to control (untreated membranes). By contrast, EPA had no significant disordering effect except when combined at equimolar levels; the EPA/DHA combination showed a reduction in ARCT to ~18 nsec at 10 mol% that was different from EPA alone (p&lt;0.05). Consistent with these findings, SAXS analysis showed DHA containing membranes had a reduced width compared to EPA by 5% or 3 Å (p&lt;0.05) due to increased trans-gauche isomerizations in the phospholipid acyl chains. Conclusion: EPA maintained membrane fluidity while DHA increased fluidity and thereby reduced membrane width due to its additional carbons and double bond. The EPA/DHA combination increased membrane fluidity compared to control and EPA alone. The disordering effects of DHA may counter EPA stabilizing effects and explain discordant clinical outcomes with different n3-FA formulations.
Abstract 13839: Value of 2D Speckle Tracking Echocardiography in Predicting Short-Term Cardiovascular Outcomes in Multisystem Inflammatory Syndrome in Children: Analysis of the MUSIC Data
Authors: Francesca Sperotto, Valiantsina Kazlova, Felicia Trachtenberg, Dongngan Truong, Sanjeev AGGARWAL, Tamara T Bradford, Joseph R Block, Sujatha Buddhe, Audrey Dionne, Andreea Dragulescu, Kanwal M Farooqi, Daniel E Forsha, Therese Giglia, Ian F Golding, Keren Hasbani, Pei-Ni Jone, Anita Krishnan, Sean Lang, Carol McFarland, Elizabeth Mitchell, Elias Moussi, Todd Nowlen, Ricardo H Pignatelli, Scott Pletzer, Ryan Serrano, Divya Shakti, Shubhika Srivastava, Thor Thorsson, Jodie Votava-Smith, Kevin G Friedman
Journal: Circulation (2023)

Introduction: Cardiovascular (CV) involvement in multisystem inflammatory syndrome in children (MISC) is frequent (80-85%). Data on 2D speckle tracking echocardiography and its value in predicting CV outcomes are limited. Hypothesis: We hypothesized that an association exists between 2D speckle tracking strain/strain rate parameters at admission and adverse CV outcomes during hospitalization (inotropic support, major arrhythmias, cardiac arrest, ECMO, death, or transplant). Methods: We performed a multicenter (33 centers) cohort study on MISC patients hospitalized from 03/2020 to 11/2021 with at least one echocardiogram read by the Core Lab. The association between each 2D speckle tracking strain parameter and adverse CV outcomes was assessed by logistic regression. Results: Of 349 patients (median age 8.7 years [IQR 5.3,12.9]), 122 (35%) had decreased left ventricle (LV) ejection fraction (EF) and 156 (45%) had depressed LV 4-chamber longitudinal strain (LS) or basal circumferential strain (CS) during hospitalization. Worst EF and strain occurred around 5 days of illness. Of those with abnormal LS or CS strain, 50% normalized in ≤1 week, 95% within 50 days. Adverse CV outcomes occurred in 121 (35%) patients. Patients with adverse outcomes were older (p=0.003), more likely to have an underlying metabolic/genetic disorder (p=0.015), abnormal troponin (p&lt;0.001), and higher C-reactive protein (CPR) at admission (p&lt;0.001). They also had higher indexed LV end-diastolic volume (p&lt;0.001) and mass (p=0.015), worse EF (p&lt;0.001), worse LS (p=0.002), and worse CS (p=0.001). When adjusting for days of illness, age, gender, race, obesity, comorbidities, SARS-CoV-2 positivity, CRP, and abnormal troponin at admission, LS Z-score (adjusted OR 1.24 [95% CI 1.03,1.49], AUC 0.754 and longitudinal early diastolic strain rate (LEDSR; adjusted OR 1.98 [IQR 1.18, 3.33], AUC 0.760) at admission were independently associated with adverse CV outcomes. Conclusion: Almost half of the MISC patients had abnormal LS or CS at admission, but the majority recovered quickly. LS and LEDSR at admission were independently associated with adverse CV outcomes. These data may help in early characterization, risk stratification, and prognostication in patients with MISC.
Abstract 19192: Deciphering the Cardioprotective Role of Ufm1 Modification in Cardiac Remodeling
Authors: Varsha Tandra
Journal: Circulation (2023)

UFM1 (ubiquitin-fold modifier 1) is a novel Ub-like protein that covalently modifies protein substrates via a highly conserved E1 (UBA5)-E2 (UFC1)-E3 (UFL1) enzymatic cascade. UFM1 modification (ufmylation) controls multiple pathophysiological events and is implicated in various human diseases. However, the significance of ufmylation in cardiac health remains poorly understood. We have previously reported that ufmylation is upregulated in compensated, hypertrophic mouse hearts but decreased in failing human hearts. Inhibition of ufmylation by targeted ablation of the E3 UFM1 ligase 1 (UFL1) in mouse hearts resulted in dilated cardiomyopathy under baseline and stress conditions. Targeted deletion of a putative UFM1 target, UFBP1, also evokes endoplasmic reticulum (ER) stress, leading to dilated cardiomyopathy While these exciting data reveal the pivotal role of ufmylation in the maintenance of ER/cardiac homeostasis, it remains unclear whether ufmylation of cardiac proteins is required for heart function and if so, how ufmylation regulates cardiac function. To determine the role of UFM1 modification in cardiomyocytes we have generated cardiac specific UFM1 CKO mice. The UFM1 CKO mice developed dilated cardiomyopathy at resting condition, as indicated by left ventricle (LV) wall thinning, chamber dilatation and impaired contractility at 4 months of age, which were further exacerbated by 6 months. To test the hypothesis that UFM1 protects the heart by modifying cardiac proteins we replenished UFM1-deficient mice with WT and conjugation deficient UFM1 via AAV9. Restoration of WT-UFM1 expression, but not the conjugation-deficient mutant, attenuated cardiac dysfunction of UFM1CKO hearts. It appears that UFM1 modification constraints pathological cardiac remodeling by maintaining ER homeostasis. Taken together, our data show that Ufmylation is a critical post-translational modification that regulates cardiac homeostasis.
Abstract 19175: Anaphylaxis After Alteplase During Treatment of Pulmonary Embolism
Authors: Cate Enstrom, Austin Roberts, Sarah Gast, Catherine Moore, Angel Cavanaugh Sharp, Brianna Garcia, Ashley Bock, Ann Gage
Journal: Circulation (2023)

Introduction: Anaphylaxis is a rare complication to alteplase, a recombinant tissue plasminogen activator (tPA), during administration for pulmonary embolism (PE). Case Presentation: A 72-year-old male with a history of necrotizing fasciitis, recent below the knee amputation, and concern for metastatic melanoma had been undergoing treatment for an acute DVT with apixaban when he presented with an extensive saddle pulmonary embolism. He was evaluated by a Pulmonary Embolism Response Team (PERT) and classified as high risk (sPESI 2, new right ventricular dysfunction, and hypoxemia) and treated with 50 mg alteplase over two hours. At the end of his infusion, he experienced worsening hypoxemia and sudden hypotension treated with fluid resuscitation and an epinephrine infusion. Hemodynamic instability was thought to be secondary to obstructive shock so an additional 50 mg of alteplase was ordered. After the initial bolus of 10 mg alteplase, the patient demonstrated signs of anaphylaxis. He was initially treated with epinephrine, diphenhydramine, famotidine, methylprednisolone, and lactated ringers for the anaphylactic shock. The patient eventually required the addition of norepinephrine, vasopressin, and methylene blue for resolution of the shock. No additional alteplase was administered and a heparin infusion was resumed for treatment of the pulmonary embolism. He was ultimately successfully weaned off vasopressors and oxygen support with resolution of the pulmonary embolism. Discussion: Cardiac critical care providers should monitor for signs of anaphylaxis when using tPA in the management of PE. The main intervention of anaphylactic shock is administration of epinephrine. Updated guidelines recommend use of intramuscular epinephrine in the setting of anaphylaxis.
Abstract 13879: Characterizing Post-Cardiac Surgery Infection Risk: A Statewide Experience
Authors: Syed Raza, Shiwei Zhou, Chiang-Hua Chang, Robert Hawkins, Raed Alnajjar, Alphonse DeLucia, Charles Schwartz, Mike P Thompson, noah barnett, Eric N Hammond, Francis D Pagani, Donald S Likosky
Journal: Circulation (2023)

Introduction: Patients undergoing cardiac surgery are at risk for developing early (in-hospital or within 30-days) and late (up to 180 days after surgery) postoperative infections. Current national database infection metrics are limited in scope and duration of follow-up. Aim: Evaluate rates and types of early and late postoperative infections and mortality. Methods: Medicare claims from 8335 Michigan fee-for-service beneficiaries undergoing isolated coronary artery bypass grafting (CABG) (n=4162), isolated surgical aortic valve replacement (SAVR) (n=618), CABG + SAVR (n=627), or transcatheter aortic valve replacement (TAVR) (n= 2946) between 2017-2020 at 33 Michigan hospitals were linked to The Society of Thoracic Surgeons data. Nine infection types were tracked within 180 days following surgery. The relationship between infections and 180-day and 365-day mortality was evaluated. Results: The average age was 74.2 ± 9.1 years, 36.5% were female, 5.0% were Black and 1.4% were Hispanic. The in-hospital infection rate was 8.9%, while 17.8% within 180 days after surgery. Infection rates varied by hospital (9.1%-33.9%), year (2017 vs 2020: 20.1% vs 16.0%), and procedure type (CABG: 18.2%, SAVR: 14.9%, CABG+SAVR: 19.6%, TAVR: 17.4%). Most common infections were urinary tract infection (8.7%), pneumonia (7.0%) and sepsis (5.2%). The overall mortality rate was 5.9% at 180-days (and varied by infection type, Table ) and 9.0% at 365 days. Patients with an infection had higher associated 180-day mortality compared to those with no infection (17.7% vs 3.4%, p&lt;0.001). Among infection types, sepsis was associated with the highest 180-day mortality rate. Conclusions: Nearly 20% of Medicare beneficiaries develop an infection within 180 days after cardiac surgery, with rates varying by 24% across hospitals and contributing to higher 180-day mortality. Future efforts should identify determinants of postoperative infections, especially given their impact on mortality.
Abstract 12539: Relationship Between the Kansas City Cardiomyopathy Questionnaire Score and New York Heart Association Class in Patients With Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM
Authors: Charles F Sherrod, Andrew Wang, Kensey L Gosch, Perry M Elliott, Neal K Lakdawala, Matthew Reaney, Yue Zhong, Jenny Lam, Kathleen W Wyrwich, John A Spertus, Andrew J Sauer
Journal: Circulation (2023)

Background: Treating hypertrophic cardiomyopathy (HCM) aims to improve health status. Given the importance of accurately assessing health status and the limitations of the New York Heart Association (NYHA) Class, the Kansas City Cardiomyopathy Questionnaire (KCCQ) has gained interest. Thus, frameworks for interpreting the KCCQ in the context of the NYHA are needed. Methods: EXPLORER-HCM (NCT03470545) randomized patients with NYHA class II-III HCM to mavacamten or placebo and collected the NYHA and KCCQ. We pooled subjects for analyses who had KCCQ scores and NYHA class at baseline and 30-weeks. KCCQ scores, stratified by class at baseline, 30 weeks, and by change in class were reported as means±standard deviations. We generated two unadjusted models predicting the probability of NYHA class attribution for a given KCCQ-Overall Summary Score (OSS) at 30 weeks and for change in NYHA class by changes in KCCQ-OSS. Results: Of 196 participants, mean age was 57.9±12.2 years, 120 (61.2%) were male, and the baseline mean LVOT gradient was 51.5±30 mm Hg. Mean KCCQ scores by NYHA classes at baseline and 30 weeks are included in Table 1. Figure 1 maps the probability of NYHA Class by KCCQ. KCCQ-OSS Scores &lt;40 mapped to Class III, scores from 40-85 mapped to Class II, and &gt;85 mapped to Class I. Reductions of &gt;25 points on the KCCQ-OSS aligned with worsening class and increases by &gt;8 points on the KCCQ-OSS reflected improvement in class. Conclusion: NYHA Class is concordant with KCCQ, but there is variability in health status within class and changes in class. These analyses may help clinicians interpret both cross-sectional and changes in KCCQ scores for patients with obstructive HCM.
Abstract 16097: Association of Neighborhood Income and Outcomes in Atrial Fibrillation: A Nationwide Retrospective Cohort Analysis
Authors: Prasanti Alekhya Kotta, VIJAY NAMBI, Arunima Misra, Mihail G Chelu, Khurram Nasir, Dmitry Abramov, Abdul Mannan Khan Minhas
Journal: Circulation (2023)

Introduction: The impact of socioeconomic status on atrial fibrillation (AF) outcomes is not well understood. We studied the association between household income and clinical outcomes in AF hospitalizations. Methods: We conducted a retrospective analysis of adult primary AF hospitalizations from the United States National Inpatient Sample (NIS) between 2016 and 2020. Quartile classification of the median household income of the zip code of the patient’s residence provided by NIS was used. Among the four income quartiles, lowest quartile was used as reference category. Weighted multivariable logistic and linear regression, adjusting for multiple patient and hospital-level characteristics (Table 1), were performed. We aimed to study patient characteristics and clinical outcomes in AF based on household income. Results: From lowest to highest income quartile, mean age and proportion of White race increased; proportion of females, Black, and Hispanic race decreased (Table 1). Compared with lowest income residents, highest income residents had lower in-hospital mortality (Odds ratio [OR] 0.78, 95% confidence interval [CI] 0.7, 0.87, P &lt; 0.001), lower disposition to care facility (OR 0.86, 95% CI 0.83-0.9, p &lt; 0.001), lower length of stay (adjusted mean difference -0.26, 95% CI -0.30, -0.22, P &lt; 0.001), higher procedure utilization including catheter and surgical ablation, atrial appendage closure, electrical cardioversion, and higher healthcare costs ($12,124 vs 10,018)(Table 1). Conclusions: We identified significantly higher adverse events and lower procedural/resource utilization in the lower-income residents compared to higher-income residents. Further research is needed to better understand these disparities, their impact on clinical outcomes, and strategies to improve healthcare disparities between SE groups.